Role of alveolar epithelial cell intercellular adhesion molecule-1 in hostdefense against Klebsiella pneumoniae

Intercellular adhesion molecule-1 (ICAM-1) is expressed at high levels on t ype I alveolar epithelial cells (AEC) in the normal alveolar space. We post ulate that AEC ICAM-1 enhances the antimicrobial activity of macrophages an d neutrophils in the alveolar space. Wild-type and mutant mice deficient in ICAM-1 were inoculated intratracheally with Klebsiella pneumoniae. After 1 0 days, 43% of the ICAM-1 mutant mice had died compared with 14% of the wil d-type controls (P = 0.003). Significantly more bacteria were isolated from lungs of ICAM-1 mutant mice than controls 24 h after inoculation (log colo ny-forming units 5.14 +/- 0.21 vs. 3.46 +/- 0.16, P = 0.001). However, neut rophil recruitment to the lung was not different. In similar experiments in the rat, inhibition of alveolar ICAM-1 by intratracheal administration of antibody resulted in significantly impaired clearance of K. pneumoniae. The role of phagocyte interactions with AEC ICAM-1 for antimicrobial activity was investigated in vitro using primary cultures of rat AEC that express ab undant ICAM-1. Alveolar macrophage phagocytosis and killing of K. pneumonia e were increased significantly in the presence of AEC; these effects were i nhibited significantly (47.5 and 52%, respectively) when AEC ICAM-1 was blo cked. Similarly, neutrophil phagocytic activity for K. pneumoniae in the pr esence of AEC in vitro was decreased when ICAM-1 on the AEC surface was blo cked. Thus in the absence of ICAM-1, there is impaired ability to clear K, pneumoniae from the lungs, resulting in increased mortality. These studies indicate that AEC ICAM-1 plays an important role in host defense against K. pneumoniae by determining the antimicrobial activity of phagocytes within the lung.